Potential Muscle-Related Biomarkers in Predicting Curve Progression to the Surgical Threshold in Adolescent Idiopathic Scoliosis-A Pilot Proteomic Study Comparing Four Non-Progressive vs. Four Progressive Patients vs. A Control Cohort.
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SUBMITTER: Wang Y
PROVIDER: S-EPMC8584606 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundAdolescent idiopathic scoliosis (AIS) is common deformity with unknown cause. Previous studies have suggested the abnormal serum leptin and ghrelin level in AIS girls. The aim of present study was to evaluate whether the serum leptin and ghrelin level could serve as risk factor in predicting the curve progression in AIS girls. The associations between them and the physical characteristics were also investigated.Materials and methodsCirculating leptin and ghrelin levels from 105 AIS girls and 40 age-matched non-AIS girls were examined by enzyme-linked immunosorbent assay. The correlations between ghrelin and leptin levels and growth-related parameters (age, weight, corrected height, corrected BMI, main Cobb angle, and Risser sign) were analyzed in AIS group. Multivariate logistic regression was used to investigate factors predicting curve progression in AIS girls.ResultsA significantly lower leptin level (6.55 ± 2.88 vs. 8.01 ± 3.12?ng/ml, p < 0.05) and a higher ghrelin level (6.33 ± 2.46 vs. 4.46 ± 2.02?ng/ml, p < 0.05) were found in all AIS patients, as compared with normal controls. Curve progression patients had a higher ghrelin level than stable curve patients (7.61 ± 2.48 vs. 5.54 ± 2.11?ng/ml, p < 0.01); for leptin level, there was no significant difference between progression and stable group. The results of multivariate logistic stepwise regression showed that premenarche status, initial main Cobb magnitude that was more than or equal to 23°, high ghrelin level (?7.30?ng/ml), and lower Risser grade (grades 0 to 2) were identified as risk factors in predicting curve progression. Ghrelin levels of >6.48?ng/ml were predictive for curve progression with 70.00 % sensitivity and 72.31 % specificity, and the area under the curve (AUC) was 0.741 (95 % confidence interval 0.646-0.821).ConclusionsHigh ghrelin level may serve as a new quantitative indicator for predicting curve progression in AIS girls.
| S-EPMC6069699 | biostudies-literature
Project description:There is no consensus on the definition of a structural proximal thoracic curve (PTC) and the indications for fusion. As such, we assessed a single institute's experience in the management of large PTCs (>35 degrees) in patients with adolescent idiopathic scoliosis (AIS) who were either fused or not fused. A retrospective radiographic analyses of 30 consecutive AIS patients with double thoracic curves who underwent PSF with a minimum of 2 years' follow-up were included for review. The patients were divided into two groups: group 1 (n = 15 patients) with fusion extended up to T2 or T3 and group 2 (n = 15) with fusion limited to T5 or below. Shoulder balance was assessed according to clavicular angle, first-rib difference, and radiographic shoulder height difference (SHD). PTCs were defined based on a Cobb angle of >35, the presence of apical rotation, and a positive T1 tilt. The decision to fuse the PTC was based on curve magnitude only, with those between 35 and 45 degrees undergoing a selective fusion of the main thoracic curve (MTC), with both curves fused if the PTC was more than 45 degrees. In group 1, there were eight females and seven males. Their ages ranged between 12 and 33 years, with a mean of 16.2 ± 5.5 years. Postoperatively, the mean PTC correction was 45.6%, which statistically differed from preoperative status (p = 0.001). No statistical difference was noted in T1 tilt and the first-rib difference from preoperative to postoperative follow-up (p > 0.05). However, the clavicular angle and SHD were increased significantly at the immediate postoperative interval (p < 0.05) but demonstrated no significant changes between the initial and the last follow-up values (p > 0.05). Group 2 consisted of one male and 14 females. The mean age was 16.4 ± 4 years (range: 11 to 28 years). The mean spontaneous PTC correction was 28.3% and remained essentially unchanged at the end of the follow-up. The improvement in the curve from preoperative status was highly statistically significant (p = 0.001). All radiographic shoulder parameters exhibited a significant increase in the immediate postoperative period and at last follow-up, and shoulder balance improvement was not noted on follow-up. Although both groups were not statistically similar with regards to the preoperative PTC, AVR, apical vertebral translation, and shoulder parameters, no significant difference could be found in PTC or shoulder parameters between both groups at last follow-up (p > 0.05). Our study illustrates important observations that should be considered in defining the PTC for fusion consideration. Spontaneous correction of the PTC occurs in structural curves greater than 35 degrees and less than 45 degrees, and this correction is maintained over time. Despite that correction, radiographic shoulder parameters are expected to slightly increase. Nonfusion strategy may be appropriate for PTCs between 35 and 45 degrees. After fusion of both the MTC and the PTC, the radiographic shoulder parameters did not significantly differ. Preoperative radiographic shoulder parameters are not predictive of postoperative shoulder imbalance.
| S-EPMC3864415 | biostudies-other
Project description:BACKGROUND:There is considerable discordance in the curve progression of adolescent idiopathic scoliosis (AIS) patients between monozygotic (MZ) twins, indicating that nongenetic factors must be involved in the curve progression of AIS patients. Epigenetic processes may constitute one of these factors and have not yet been investigated in relation to curve progression in AIS patients. METHODS:The genome and methylome of peripheral monocytes were compared between MZ twins discordant for curve progression. Sets of differentially methylated sites were validated using the MassARRAY platform of Sequenome on additional samples. RESULTS:In the discovery study, we found evidence suggesting a lack of differences at the genome sequence level and the presence of epigenetic differences related to the curve progression of AIS patients. The top 4 differentially methylated CpG sites associated with curve severity were tested, and only site cg01374129 (CpG site located at chr8:122583383, Hg19) was confirmed in two replication cohorts. The methylation levels of site cg01374129 were significantly lower in the progression group than in the nonprogression group. Cox regression analysis demonstrated that hypo-methylation of site cg01374129 was an independent prognostic factor for curve severity. Site cg01374129 methylation as a marker achieved a sensitivity of 76.4% and a specificity of 85.6% in differentiating between samples from patients with and without curve progression (AUC?=?0.827; 95% CI: 0.780 to 0.876). CONCLUSION:Increased curvature is associated with decreased methylation at site cg01374129. Our results indicate that methylation of site cg01374129 may therefore serve as a promising biomarker in differing between patients with and without curve progression.
| S-EPMC6197569 | biostudies-literature
Project description:Background:In adolescent idiopathic scoliosis (AIS), the continuous search for effective prognostication of significant curve progression at the initial clinical consultation to inform decision for timely treatment and to avoid unnecessary overtreatment remains a big challenge as evidence of the multifactorial etiopathogenic nature is increasingly reported. This study aimed to formulate a composite model composed of clinical parameters and circulating markers in the prediction of curve progression. Method:This is a two-phase study consisting of an exploration cohort (120 AIS, mean Cobb angle of 25°± 8.5 at their first clinical visit) and a validation cohort (51 AIS, mean Cobb angle of 23° ± 5.0° at the first visit). Patients with AIS were followed-up for a minimum of six years to formulate a composite model for prediction. At the first visit, clinical parameters were collected from routine clinical practice, and circulating markers were assayed from blood. Finding:We constructed the composite predictive model for curve progression to severe Cobb angle > 40° with a high HR of 27.9 (95% CI of 6.55 to 119.16). The area under curve of the composite model is higher than that of individual parameters used in current clinical practice. The model was validated by an independent cohort and achieved a sensitivity of 72.7% and a specificity of 90%. Interpretation:This is the first study proposing and validating a prognostic composite model consisting of clinical and circulating parameters which could quantitatively evaluate the probability of curve progression to a severe curvature in AIS at the initial consultation. Further validation in clinic will facilitate application of composite model in assisting objective clinical decision.
| S-EPMC6948250 | biostudies-literature
Project description:BackgroundThere is an acknowledged discrepancy between radiographic and cosmetic parameters for patients with adolescent idiopathic scoliosis (AIS). However, no study has specifically evaluated cosmesis in patients with congenital scoliosis (CS). Therefore, the purpose of this study was to identify the cosmetic differences between patients with CS and case-matched patients with AIS and to investigate the correlation between radiological measurements and clinical cosmetic assessment indices.MethodsA total of 37 adolescents with CS and 37 sex-, age-, and curve magnitude-matched patients with AIS were included. Cobb angle, shoulder height difference (SHD), coronal balance (CB), T1 tilt, first rib angle (FRA), clavicle angle (CA), clavicle-rib cage intersection (CRCI), and apical vertebra translation (AVT) were measured in the full X-ray of the spine. Shoulder area index 1 (SAI1), shoulder area index 2 (SAI2), shoulder angle (SA), axilla angle (AA), thoracolumbar area index (TLAI), and right and left waist angle difference (RLWAD) were measured on the clinical images from a posterior view. Hump index (HI) was measured in the forward bending photography. All patients completed the Scoliosis Research Society-22 (SRS-22) questionnaire.ResultsNo significant difference was noted in the radiographic parameters between the AIS and CS groups (P>0.05). However, patients with CS exhibited significantly lower SAI1 (0.91 vs. 0.98; P=0.002) and SAI2 (0.85 vs. 0.95; P=0.001) than did the patients with AIS. The SRS-22 scores for self-image and mental health in patients with CS were significantly lower than those in patients with AIS (P<0.05). The correlation coefficients with statistical significance between radiographic and cosmetic measurements in patients with CS and those with AIS ranged from -0.493 to 0.534 and from -0.653 to 0.717, respectively. None of the correlation coefficients exceeded 0.8, indicating that the current radiological indices only exhibited a limited level of consistency with patients' cosmesis.ConclusionsAs compared with age-, gender-, and curve pattern-matched patients with AIS, patients with CS exhibited worse cosmesis and had clinically significantly lower SRS-22 scores despite having relatively small clinical differences. Although the radiographic parameters may not always align with clinical presentation, this discrepancy could be observed in both patients with CS and those with AIS.
| S-EPMC10498239 | biostudies-literature
Project description:PurposeBrace treatment is the most common nonoperative treatment to prevent curve progression in adolescent idiopathic scoliosis (AIS). The goal of this review and analysis is to characterize curve behavior after completion of brace treatment and to identify factors that may facilitate the estimation of long-term curve progression.MethodA review of the English language literature was completed using the MEDLINE (PUBMED) database of publications after 1990 until September 2020. Studies were included if they detailed a minimum of 1 year post-brace removal follow-up of AIS patients. Data retrieved from the articles included Cobb angle measurements of the major curves at "in-brace," weaning, and follow-up visit(s) for all patients described and for subset populations.ResultsFrom 75 articles, 18 relevant studies describing a follow-up period of 1-25 years following brace removal were included in the analyses. The reviewed literature demonstrates that curves continue to progress after brace treatment is completed with three main phases of progression: (i) immediate (upon brace removal) where a mean curve progression of 7° occurs; (ii) short term (within five years of brace removal) where a relatively high progression rate is evident (0.8°/year); and (iii) long term (more than five years after brace removal) where the progression rate slows (0.2°/year). The magnitude and rate of curve progression is mainly dependent on the degree of curve at weaning as curves weaned at < 25° progress substantially less than curves weaned at ≥ 25° at 25 years.ConclusionCurves continue to progress after brace removal and the rate and magnitude of progression are associated with the curve size at weaning, with larger curves typically exhibiting more rapid and severe progression. This analysis provides physicians and patients the ability to estimate long-term curve size based on the curve size at the time of weaning.Level of evidenceIV.
| S-EPMC10147768 | biostudies-literature
Project description:Recent studies have shown an association between osteopenia and adolescent idiopathic scoliosis (AIS) and implied that osteopenia plays a causative role in AIS development. This study aimed to determine if minodronate (MIN) treatment could prevent curve progression by increasing bone mass in a thoracic restraint (TR) mouse model, which develops causes the development of thoracic scoliosis similar to human AIS. A total of 100 young female C57BL6J mice were divided into four groups: (1) control with vehicle (CON/VEH; n = 20), (2) control with MIN (CON/MIN; n = 20), (3) TR with vehicle (TR/VEH; n = 30), or (4) TR with MIN (TR/MIN; n = 30). MIN (0.01 mg/kg/week) and vehicle were administered intraperitoneally to their respective groups. TR was performed at age 4 weeks, and the mice were sacrificed at age 9 weeks. Body weights, spine radiographs, femoral bone mineral density (BMD), serum bone marker levels, and histomorphometry of the cancellous bone of the thoracic vertebrae were analyzed. TR significantly reduced weight gain in the TR/VEH group relative to the CON/VEH group. TR also induced osteoporosis with accelerated bone resorption, as indicated by decreases in femoral BMDs and thoracic cancellous bone volume and increases in serum bone resorption marker levels and histomorphometric resorption parameters in the TR/VEH group. MIN partially improved body weight gain and improved poor bone structure relative to the TR/VEH group by suppressing high bone resorption in the TR/MIN mice. MIN significantly reduced the curve magnitudes, as indicated by a 43% lower curve magnitude in the TR/MIN mice than in the TR/VEH mice (17.9 ± 8.9° vs. 31.5 ± 13.1°; p< 0.001). The administration of MIN increased bone mass and reduced the severity of scoliosis in the TR mice. MIN was suggested as a possible inhibitor of scoliosis development.
| S-EPMC6107151 | biostudies-literature
Project description:Schroth exercises for scoliosis are prescribed based on curve types. This study aimed to determine the reliability of an algorithm for classifying Schroth curve types. Forty-four consecutive volunteers with adolescent idiopathic scoliosis, 10 to 18 years old, with curves 10° to 50°, were recruited from a scoliosis clinic. Their standing posture and Adam's bending test were videotaped. Ten consecutive Schroth therapist volunteers from an international registry independently classified the curve types using the proposed classification algorithm. Videos were rated twice at least seven days apart. Reliability was calculated using the Gwet's AC1 agreement coefficient for all the raters and for subgroups reporting full understanding (well-trained) and with prior algorithm experience. The intra-rater and weighted agreement coefficients for all the raters were 0.64 (95% CI: 0.53-0.73) and 0.75 (0.63-0.84), respectively. For the well-trained raters, they were 0.70 (0.60-0.78) and 0.82 (0.73-0.88), respectively; for the experienced raters, they were 0.81 (0.77-0.85) and 0.89 (0.80-0.94), respectively. The inter-rater versus weighted agreement coefficients for all the raters were 0.43 (0.28-0.58) versus 0.48 (0.29-0.67). For the well-trained raters, they were 0.50 (0.38-0.61) versus 0.61 (0.49-0.72), and for the experienced raters, they were 0.67 (0.50-0.85) versus 0.79 (0.64-0.94). Full understanding and experience led to higher reliability. Use of the algorithm can help standardize Schroth exercise treatment.
| S-EPMC10047876 | biostudies-literature
Project description:BackgroundThe Proximal Femur Maturity Index (PFMI) can be used to assess skeletal maturity on existing whole-spine radiographs without additional radiation. However, the relationship between the PFMI at the initiation of bracing for adolescent idiopathic scoliosis (AIS) and subsequent curve progression remains unknown. This study aimed to investigate the relationship between the PFMI and curve progression, and the predictability of risks to adulthood curve progression and surgical thresholds based on the PFMI grade at brace initiation.MethodsThis was a prospective study of 202 patients with AIS who were prescribed underarm bracing according to the Scoliosis Research Society criteria and had good brace-wear compliance. The patients were followed from brace initiation until complete skeletal maturity. Longitudinal data on the coronal Cobb angle and skeletal maturity assessments using Risser staging, Sanders staging, the distal radius and ulna classification, and the PFMI were collected. Each patient was assessed on whether the major curve progressed to ≥40° (adulthood deterioration) and ≥50° (the surgical threshold). Logistic regressions were used to predict probabilities of curve progression to the 2 thresholds, adjusted for factors that were significant in univariate analyses.ResultsThe PFMI correlated with the other skeletal maturity indices (r s [Spearman rank correlation] = 0.60 to 0.72, p < 0.001 for all). The pre-brace PFMI grade correlated with progression to ≥40° (r rb [rank-biserial correlation] = -0.30, p < 0.001) and to ≥50° (r rb = -0.20, p = 0.005). Based on regression models (p < 0.001) adjusted for the pre-brace major Cobb angle and curve type, brace initiation at PFMI grades 2 and 3 for a curve of ≥30° had predicted risks of 30% (95% confidence interval [CI], 4% to 55%) and 12% (95% CI, 7% to 17%), respectively, for progression to the surgical threshold. Brace initiation at PFMI grade 5 had 0% progression risk.ConclusionsThe PFMI can be used for predicting curve progression and prognosticating brace outcomes in AIS. Patients with brace initiation at PFMI grade 4 for a curve of <30° or at grade 5 were unlikely to progress to the adulthood deterioration or surgical threshold. In comparison, skeletally immature patients initiating bracing at a PFMI grade of ≤3 for a major curve of ≥30° had a higher risk of progression despite compliant brace wear.Level of evidencePrognostic Level II . See Instructions for Authors for a complete description of levels of evidence.
| S-EPMC10939470 | biostudies-literature
Project description:ObjectiveTo investigate whether single nucleotide polymorphisms (SNP) of the calmodulin1 (CALM1) and estrogen receptor-α genes correlate with double curve in adolescent idiopathic scoliosis (AIS).MethodsA total of 67 Chinese patients with AIS with double curve and 100 healthy controls were recruited. Curve pattern and Cobb angle of each patient were recorded. The Cobb angle is at least 30°. There were 60 patients with Cobb angle ≥ 40°. According to the apical location of the major curve, there were 40 thoracic curve patients. Four polymorphic loci, including rs12885713 (-16C > T) and rs5871 in the CALM1 gene and rs2234693 (Pvu II) and rs9340799 (Xba I) in the estrogen receptor 1 (ER1) gene were analyzed by the ABI3730 genetic analyzer.ResultsThe current study indicates that: (i) there are statistical differences between patients with double curve, with Cobb angle ≥ 40° and with thoracic curve and healthy controls in the polymorphic distribution of the rs2234693 site of the ER1 gene, (P= 0.014, 0.0128, 0.0184 respectively); (ii) there is a difference between patients with double curve and controls in the polymorphic distribution of the rs12885713 site in the CALM1 gene (P= 0.034); and (iii) there is a difference between thoracic curve patients and controls in the polymorphic distribution of the rs5871 site in the CALM1 gene (P= 0.0102).ConclusionsDifferent subtypes of AIS might be related to different SNP. A combination of CALM1 and ER1 gene polymorphisms might be related to double curve in patients with AIS. Further study is necessary to confirm these hypotheses.
| S-EPMC6583290 | biostudies-literature